title: Biological characterization of the antiproliferative potential of Co(II) and Sn(IV) coordination compounds in human cancer cell lines: a comparative proteomic approach.
abstract: BACKGROUND
  The discovery of cisplatin's antitumor activity led to a great interest in the potential application of coordination compounds as chemotherapeutic agents. It is essential to identify new compounds that selectively inhibit tumor proliferation, evading secondary effects and resistance associated with chemotherapeutics.
  
  
  METHODS
  The in vitro antiproliferative potential of an organotin(IV) compound was evaluated using colorectal and hepatocellular carcinoma, mammary gland adenocarcinoma cell lines, and human fibroblasts. Tumor cell death was evaluated by fluorescence microscopy and flow cytometry for the Sn(IV) compound and also for a Co(II) compound bearing 1,10-phenanthroline-5,6-dione as ligand. Comparative proteomic analysis for both compounds was assessed in the colorectal cancer cell line.
  
  
  RESULTS
  The Sn(IV) compound presented a high cytotoxic effect in colorectal and hepatocellular carcinoma cell lines (IC50 of 0.238 ± 0.011 μM, 0.199 ± 0.003 μM, respectively), and a lower cytotoxicity in human fibroblasts. Both compounds induced cell apoptosis and promoted the overexpression of oxidative stress-related enzyme superoxide dismutase [Cu-Zn] (SODC). The Co(II) compound induced a decreased expression of anti-apoptotic proteins (translationally-controlled tumor protein and endoplasmin), and the Sn(IV) compound decreased expression of proteins involved in microtubule stabilization, TCTP, and cofilin-1.
  
  
  CONCLUSIONS
  Our data reveals a high in vitro antiproliferative potential against cancer cell lines and a moderate selectivity promoted by the Sn(IV) compound. Proteomic analysis of Sn(IV) and Co(II) compounds in the colorectal cancer cell line allowed an insight to their mechanisms of action, particularly by affecting the expression of proteins typically deregulated in cancer, and also suggesting a promising therapeutic potential for both compounds.
authors.forename: Ana
authors.initials: A
authors.lastname: Silva
authors.forename: Daniel
authors.initials: D
authors.lastname: Luís
authors.forename: Susana
authors.initials: S
authors.lastname: Santos
authors.forename: Joana
authors.initials: J
authors.lastname: Silva
authors.forename: Ana Soraia
authors.initials: AS
authors.lastname: Mendo
authors.forename: Lidia
authors.initials: L
authors.lastname: Coito
authors.forename: Telma F S
authors.initials: TF
authors.lastname: Silva
authors.forename: Maria Fatima C Guedes
authors.initials: MF
authors.lastname: da Silva
authors.forename: Luísa M D R S
authors.initials: LM
authors.lastname: Martins
authors.forename: Armando J L
authors.initials: AJ
authors.lastname: Pombeiro
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Borralho
authors.forename: Cecília M P
authors.initials: CM
authors.lastname: Rodrigues
authors.forename: Maria Guadalupe
authors.initials: MG
authors.lastname: Cabral
authors.forename: Paula A
authors.initials: PA
authors.lastname: Videira
authors.forename: Carolino
authors.initials: C
authors.lastname: Monteiro
authors.forename: Alexandra R
authors.initials: AR
authors.lastname: Fernandes
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003035:Cobalt / Q000494:pharmacology*; D056831:Coordination Complexes / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects; D045325:HCT116 Cells / Q000187:drug effects; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009947:Organotin Compounds / Q000494:pharmacology*; D040901:Proteomics; D000090324:Tumor Protein, Translationally-Controlled 1
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D009947:Organotin Compounds; C000715647:TPT1 protein, human; D000090324:Tumor Protein, Translationally-Controlled 1; D003035:Cobalt